Hepatoprotective effect of Maytenus robusta Reiss extract on CCl4-induced hepatotoxicity in mice and HepG2 cells.

We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl4 in mice promoted a deep destruction of the histological lobular structure and increased the alanine aminotransferase (ALT) serum levels by 46.25% compared with the control group (p < 0.05). The M. robusta extract reduced the hepatic histological changes and normalization the ALT levels. The antioxidant effect of M. robusta in liver tissue promoted the reduction in 31.5% on lipoperoxides levels (p < 0.05), increased by 101.5% the reduced glutathione content (p < 0.05) and increased the activity of superoxide dismutase, catalase, and glutathione-S-transferase by 21.3% (p < 0.05), 49.3% (p < 0.05), and 27.6% (p < 0.05), respectively, compared with the vehicle group. Moreover, the extract reduced hepatic inflammation by diminishing myeloperoxidase activity, TNF and interleukin-6 levels by 29.4% (p < 0.05), 46.1% (p < 0.01), and 59.5% (p < 0.0001), respectively, compared with the vehicle group. The viability of HepG2 cells after incubation with CCl4 was 29.56± 3.07%, whereas the extract (300 µg/mL) restored the viability to 65.27± 8.75% and aspartate aminotransferase levels to 41.82 ± 4.41 U/L. The extract scavenged DPPH (IC50 = 14.44 µg/mL) and ABTS (IC50 = 3.00 µg/mL) radicals and did not produce acute toxicity in mice at 2000 mg/kg. In conclusion, was confirmed the hepatoprotective potential of M. robusta by its antioxidant effects.

Establishing national clinical diagnostic reference levels and achievable doses for CT examinations in Brazil: A prospective study.

PURPOSE: Diagnostic reference levels (DRL) and achievable doses (AD) are important tools for radiation dose optimization. Therefore, a prospective study was performed which aimed to establish a multi-parametric, clinical indication based - DRL(DRLCI) and clinical indication - AD (ADCI) for adult CT in Brazil. METHODS: The prospective study included 4787 patients (50 ± 18 years old; male:female 2041:2746) at 13 Brazilian sites that have been submitted to head, paranasal sinus, cervical spine, chest, or abdomen-pelvis CT between January and October 2021 for 13 clinical indications. The sites provided the following information: patient age, gender, weight, height, body mass index[BMI], clinical indications, scanner information(vendor, model, detector configuration), scan parameters (number of scan phases, kV, mA, pitch) and dose-related quantities (CT dose index volume- CTDIvol, dose length product- DLP). Median(AD) and 75th(DRL) percentile CTDIvol and DLP values were estimated for each body region and clinical indications. Non-normal data were analyzed with the Kruskal-Wallis test. RESULTS: In majority of Brazilian sites, body region and clinical indications based DRLs were at or lower than the corresponding DRLs in the US and higher than Europe. Although radiation doses varied significantly for patients in different body mass index groups (p < 0.001), within each body region, there were no differences in radiation doses for different clinical indications (p > 0.1). Radiation doses for 7/13 clinical indications were higher using iterative reconstruction technique than for the filtered back projection. CONCLUSIONS: There was substantial variation in Brazil DRLCI across different institutions with higher doses compared to the European standards. There was also a lack of clinical indication-based protocol and dose optimization based on different clinical indications for the same body region.

Improvement in phloroglucinol compound extracted from different parts of Eugenia umbelliflora monitored by LC-UV and antimicrobial activity.

The phloroglucinol eugenial C, eugenial D and eugenial E are the main active compounds in Eugenia umbelliflora fruits. This study aims to evaluate the extraction conditions of E. umbelliflora, using ethanol as solvent, focusing on the phloroglucinol and antimicrobial activity. In order to optimize the extraction conditions, ethanol 50, 70 and 90 oGL was used as a solvent in the proportions of 1:20 (w/v) of drug:solvent ratio (D:S), stirring (330 rpm) at room temperature during 4 h, monitored by LC-UV and antimicrobial assay. The LC-UV method developed was linear over a concentration range of 3.4-68.0, 5.3-106.0 and 5.0-100.8 µg.mL-1 of eugenial C, eugenial D and eugenial E, having LOQ of 1.68, 1.33 and 0.8 µg.mL-1, respectively. The fruits showed the best herbal raw material and showed the highest phloroglucinol concentration and activity against S. aureus, when extracted with ethanol 90oGL, during 4 h, at 1:20 of D:S.

Antioxidant idebenone-loaded nanoparticles based on chitosan and N-carboxymethylchitosan.

Nanoparticles based on chitosan (Ch) and N-carboxymethylchitosan (N-CMCh) cross-linked with tripolyphosphate (TPP) were developed by co-drying with idebenone in different polymer-to-drug ratios (1.3:1 to 16:1) with 20% (wt/wt) colloidal silicon dioxide and tripolyphosphate (0.2 mg/mL). At high ratios (8:1 and 16:1) the spray-dried powder showed spherical and dense particles with a size close to 1 µm, allowing almost complete drug coating by the polymeric system and a high efficiency of drug incorporation (>90% and >80%, for Ch and N-CMCh, respectively). The nanoparticles showed a 10-fold increase of drug stability in comparison with free drug and preserved antioxidant activity in vitro. Compared with the severely irritative free form of idebenone, the nanoparticle formulation showed decreased mucous membrane irritation. These results revealed the potential of Ch and N-CMCh nanoparticles as carriers for a hydrophobic and irritative drug such as idebenone for topical or nasal use.

Hydroalcoholic extract of Sapium glandulatum (Vell.) Pax displays potent anti-inflammatory activities through a glucocorticoid receptor-dependent pathway.

BACKGROUND: Ethnobotanical studies of the Sapium genus reveal that many species are widely used in several countries as therapeutic drugs and they are widely used in folk medicine for treatment of different diseases, including skin inflammation. This raises interest in the study of the pharmacological properties and phytochemical composition of these plants. The biological properties of Sapium glandulatum, a native species of southern Brazil, has not been reported in the literature. PURPOSE: The aim of the present study was to investigate the anti-inflammatory action of the hydroalcoholic extract of Sapium glandulatum (EHSG) leaves in mouse models of acute or chronic skin inflammation. STUDY DESIGN/METHODS: Topical effects of EHSG were evaluated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema in the ear. Systemic effects of the extract were studied in a TPA-induced ear edema model, as well as in a carrageenan-induced paw edema model. To gain insight into the mechanism by which EHSG blocked inflammation, we evaluated the role of glucocorticoid receptors (GR) using the TPA-induced ear edema model and also measured specific binding in a glucocorticoid assay. Possible adverse effects of EHSG were evaluated after multiple treatments with the extract in the skin atrophy model on the ear and with the alkaline comet assay. RESULTS: EHSG presented potent anti-inflammatory activity when applied topically in acute and chronic models, inhibiting edema formation and leukocyte migration as well as expression pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α in the tissue. Similar anti-inflammatory effects were found following oral treatment in both ear and paw edema models. Strikingly, the EHSG-induced blockade of leukocyte migration was reversed by mifepristone, a GR antagonist. Additionally, a specific binding assay revealed that ESGH interacts with GR. Multiple treatments with EHSG failed to induce adverse effects when evaluated in the skin atrophy model and bone marrow genotoxicity test. CONCLUSION: Taken together, our data suggest that EHSG is a potential source of anti-inflammatory tool compounds for the treatment of pro-inflammatory-derived skin diseases, and its mechanism of action may be, at least in part, via the GR pathway.